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Importance: High visit-to-visit blood pressure variability (BPV) in late life may reflect increased dementia risk better than mean systolic blood pressure (SBP). Evidence from midlife to late life could be crucial to understanding this association., Objective: To determine whether visit-to-visit BPV at different ages was differentially associated with lifetime incident dementia risk in community-dwelling individuals., Design, Setting, and Participants: This cohort study analyzed data from the Adult Changes in Thought (ACT) study, an ongoing population-based prospective cohort study in the US. Participants were 65 years or older at enrollment, community-dwelling, and without dementia. The study focused on a subset of deceased participants with brain autopsy data and whose midlife to late-life blood pressure data were obtained from Kaiser Permanente Washington medical archives and collected as part of the postmortem brain donation program. In the ACT study, participants underwent biennial medical assessments, including cognitive screening. Data were collected from 1994 (ACT study enrollment) through November 2019 (data set freeze). Data analysis was performed between March 2020 and September 2023., Exposures: Visit-by-visit BPV at ages 60, 70, 80, and 90 years, calculated using the coefficient of variation of year-by-year SBP measurements over the preceding 10 years., Main Outcomes and Measures: All-cause dementia, which was adjudicated by a multidisciplinary outcome adjudication committee., Results: A total of 820 participants (mean [SD] age at enrollment, 77.0 [6.7] years) were analyzed and included 476 females (58.0%). A mean (SD) of 28.4 (8.4) yearly SBP measurements were available over 31.5 (9.0) years. The mean (SD) follow-up time was 32.2 (9.1) years in 27 885 person-years from midlife to death. Of the participants, 372 (45.4%) developed dementia. The number of participants who were alive without dementia and had available data for analysis ranged from 280 of those aged 90 years to 702 of those aged 70 years. Higher BPV was not associated with higher lifetime dementia risk at age 60, 70, or 80 years. At age 90 years, BPV was associated with 35% higher dementia risk (hazard ratio [HR], 1.35; 95% CI, 1.02-1.79). Meta-regression of HRs calculated separately for each age (60-90 years) indicated that associations of high BPV with higher dementia risk were present only at older ages, whereas the association of SBP with dementia gradually shifted direction linearly from being incrementally to inversely associated with older ages., Conclusions and Relevance: In this cohort study, high BPV indicated increased lifetime dementia risk in late life but not in midlife. This result suggests that high BPV may indicate increased dementia risk in older age but might be less viable as a midlife dementia prevention target.

Importance: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients., Objective: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment., Design, Setting, and Participants: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022., Intervention: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target., Main Outcomes and Measures: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI., Results: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk., Conclusions and Relevance: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion., Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Importance: The cardiovascular and renal outcomes of angiotensin-II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatment are well-known; however, few studies have evaluated initiation of these agents and cognitive impairment., Objective: To emulate a target trial to evaluate the cognitive outcomes of initiating an ARB- vs ACEI-based antihypertensive regimen in individuals at risk for mild cognitive impairment (MCI) and probable dementia (PD)., Design, Setting, and Participants: Active comparator, new-user observational cohort study design using data from the Systolic Blood Pressure Intervention Trial (SPRINT), conducted November 2010 through July 2018. Marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions were estimated with inverse probability (IP) weighting to account for confounding. Participants were using neither an ARB nor ACEI at baseline. Data analysis was conducted from April 7, 2021, to April 26, 2022., Exposures: New users of ARB vs ACEI during the first 12 months of trial follow-up., Main Outcomes and Measures: Composite of adjudicated amnestic MCI or PD., Results: Of 9361 participants, 727 and 1313 new users of an ARB or ACEI, respectively, with well-balanced baseline characteristics between medication exposure groups after inverse probability weighting (mean [SD] age, 67 [9.5] years; 1291 ]63%] male; 240 [33%] Black; 89 [12%] Hispanic; 383 [53%] White; and 15 [2%] other race or ethnicity. In the primary analysis, during a median follow-up of 4.9 years, the inverse probability-weighted rate of amnestic MCI or PD was 4.3 vs 4.6 per 100 person-years among participants initiating ARB vs ACEI (HR, 0.93; 95% CI, 0.76-1.13). In subgroup analyses, new users of an ARB vs ACEI had a lower rate of amnestic MCI or PD among those in the standard systolic blood pressure treatment arm (HR, 0.61; 95% CI, 0.41-0.91) but not in the intensive arm (HR, 1.17; 95% CI, 0.90-1.52) (P = .007 for interaction)., Conclusions and Relevance: In this observational cohort study of US adults at high cardiovascular disease risk, there was no difference in the rate of amnestic MCI or PD among new users of an ARB compared with ACEI, although 95% CIs were wide.

Importance: The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown., Objective: To investigate whether the association between SBP and dementia risk is U-shaped and whether age and comorbidity play a role in this association., Design, Setting, and Participants: This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021., Exposures: Baseline systolic BP., Main Outcomes and Measures: All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders [Third Edition Revised] or Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines., Results: The study analyzed 7 cohort studies with a total of 17 286 participants, among whom 10 393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P = .001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 [95% CI, 152-178] mm Hg to 170 [95% CI, 160-260] mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P < .001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P = .03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P < .001) and 166 mm Hg (95% CI, 154-260 mm Hg; P = .02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct., Conclusions and Relevance: This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.

Background: One's experience with dementia may affect their perceptions about dementia preventability, which in turn could influence preventive health behaviors. We aimed to examine how having a family history of dementia and caregiving experience are associated with perceptions about and self-efficacy for dementia preventability., Methods: Cross-sectional, self-administered survey. Participants reported whether they have had a family member with dementia and, among those who reported having a family member with dementia, whether they served as a caregiver. Outcomes were perceptions about the likelihood of dementia preventability, self-efficacy for dementia prevention, and benefits of specific dementia prevention strategies. Associations were assessed via partial proportional odds model for ordinal outcome variables and logistic regression for binary outcome variables., Results: Of 1,575 respondents, 71% had a family member with dementia, of which 42% served as a caregiver. People with a family member with dementia were less likely to believe that dementia is preventable (aOR = 0.75, 95% CI: 0.58, 0.96) and had lower self-efficacy for dementia prevention (aOR = 0.71, 95% CI: 0.56, 0.90). The subgroup analysis among those with caregiving experience was consistent with the primary findings, showing less belief in the likelihood of dementia preventability (aOR = 0.69, 95% CI: 0.46, 1.03) and self-efficacy (aOR = 0.75, 95% CI: 0.56, 1.00)., Conclusion: Having a family member with dementia is associated with unfavorable perceptions about dementia preventability. Incorporating family history of dementia into communication efforts about dementia risk reduction may help address potential barriers to preventive health behaviors.

Importance: Use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, this association with cognitive outcomes in hypertension trials, with blood pressure levels in the range of current guidelines, has not been evaluated., Objective: To examine the association between use of exclusively antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors on mild cognitive impairment (MCI) or dementia., Design, Setting, and Participants: This cohort study is a secondary analysis (April 2011 to July 2018) of participants in the randomized Systolic Blood Pressure Intervention Trial (SPRINT), which recruited individuals 50 years or older with hypertension and increased cardiovascular risk but without a history of diabetes, stroke, or dementia. Data analysis was conducted from March 16 to July 6, 2021., Exposures: Prevalent use of angiotensin II receptor type 2 and 4-stimulating or -inhibiting antihypertensive medication regimens at the 6-month study visit., Main Outcomes and Measures: The primary outcome was a composite of adjudicated amnestic MCI or probable dementia., Results: Of the 8685 SPRINT participants who were prevalent users of antihypertensive medication regimens at the 6-month study visit (mean [SD] age, 67.7 [11.2] years; 5586 [64.3%] male; and 935 [10.8%] Hispanic, 2605 [30.0%] non-Hispanic Black, 4983 [57.4%] non-Hispanic White, and 162 [1.9%] who responded as other race or ethnicity), 2644 (30.4%) were users of exclusively stimulating, 1536 (17.7%) inhibiting, and 4505 (51.9%) mixed antihypertensive medication regimens. During a median of 4.8 years of follow-up (95% CI, 4.7-4.8 years), there were 45 vs 59 cases per 1000 person-years of amnestic MCI or probable dementia among prevalent users of regimens that contained exclusively stimulating vs inhibiting antihypertensive medications (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87). When comparing stimulating-only vs inhibiting-only users, amnestic MCI occurred at rates of 40 vs 54 cases per 1000 person-years (HR, 0.74; 95% CI, 0.64-0.87) and probable dementia at rates of 8 vs 10 cases per 1000 person-years (HR, 0.80; 95% CI, 0.57-1.14). Negative control outcome analyses suggested the presence of residual confounding., Conclusions and Relevance: In this secondary analysis of SPRINT, prevalent users of regimens that contain exclusively antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors had lower rates of incident cognitive impairment. Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline.

Objective: To assess whether angiotensin II-stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II-inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the "angiotensin hypothesis.", Methods: We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6-8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70-78 (mean 74.5 ± 2.5) years., Results: After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II-stimulating, 8.2% (59/721) in angiotensin II-inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II-stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34-0.89) without excess mortality (HR, 0.86; 95% CI, 0.64-1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53-1.20) without excess mortality (HR, 0.97; 95% CI, 0.76-1.24), compared to angiotensin II-inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease., Conclusions: Users of angiotensin II-stimulating antihypertensives had lower dementia rates compared to angiotensin II-inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Higher glucose levels are associated with dementia risk in people with and without diabetes. However, little is known about how this association might vary by hypertension status and antihypertensive treatment. Most studies on modifiable dementia risk factors consider each factor in isolation., Objective: To test the hypothesis that hypertension and antihypertensive treatments may modify associations between glucose levels and dementia., Methods: Analyses of data generated from a research study and clinical care of participants from a prospective cohort of dementia-free older adults, including glucose measures, diabetes and antihypertensive treatments, and blood pressure data. We defined groups based on blood pressure (hypertensive versus not, ≥140/90 mmHg versus <140/90 mmHg) and antihypertensive treatment intensity (0, 1, or ≥2 classes of antihypertensives). We used Bayesian joint models to jointly model longitudinal exposure and time to event data., Results: A total of 3,056 participants without diabetes treatment and 480 with diabetes treatment were included (mean age at baseline, 75.1 years; mean 7.5 years of follow-up). Higher glucose levels were associated with greater dementia risk among people without and with treated diabetes. Hazard ratios for dementia were similar across all blood pressure/antihypertensive treatment groups (omnibus p = 0.82 for people without and p = 0.59 for people with treated diabetes)., Conclusion: Hypertension and antihypertensive treatments do not appear to affect the association between glucose and dementia risk in this population-based longitudinal cohort study of community-dwelling older adults. Future studies are needed to examine this question in midlife and by specific antihypertensive treatments.

Background: Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer's disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD., Objective: Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity., Methods: Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities)., Results: Among persons diagnosed with ADRD or related symptoms, 33.3% used an approved drug over the study period. Odds of use was higher among Whites than non-Whites. Among ADRD drug users, 40% initiated use within 6 months of the initial ADRD or related symptoms diagnosis, and 16% initiated prior to a diagnosis. We observed disparities by race/ethnicity: 28% of Asians, 24% of Hispanics, 16% of Blacks, and 15% of Whites initiated prior to diagnosis., Conclusions: The use of antidementia drugs is relatively low and varies widely by race/ethnicity. Heterogeneity in timing of initiation and use may affect health and cost outcomes, but these effects merit further study.

Objectives: Early recognition of dementia would allow patients and their families to receive care earlier in the disease process, potentially improving care management and patient outcomes, yet nearly half of patients with dementia are undiagnosed. Our aim was to develop and validate an electronic health record (EHR)-based tool to help detect patients with unrecognized dementia (EHR Risk of Alzheimer's and Dementia Assessment Rule [eRADAR])., Design: Retrospective cohort study., Setting: Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system., Participants: A total of 16 665 visits among 4330 participants in the Adult Changes in Thought (ACT) study, who undergo a comprehensive process to detect and diagnose dementia every 2 years and have linked KPWA EHR data, divided into development (70%) and validation (30%) samples., Measurements: EHR predictors included demographics, medical diagnoses, vital signs, healthcare utilization, and medications within the previous 2 years. Unrecognized dementia was defined as detection in ACT before documentation in the KPWA EHR (ie, lack of dementia or memory loss diagnosis codes or dementia medication fills)., Results: Overall, 1015 ACT visits resulted in a diagnosis of incident dementia, of which 498 (49%) were unrecognized in the KPWA EHR. The final 31-predictor model included markers of dementia-related symptoms (eg, psychosis diagnoses, antidepressant fills), healthcare utilization pattern (eg, emergency department visits), and dementia risk factors (eg, cerebrovascular disease, diabetes). Discrimination was good in the development (C statistic = .78; 95% confidence interval [CI] = .76-.81) and validation (C statistic = .81; 95% CI = .78-.84) samples, and calibration was good based on plots of predicted vs observed risk. If patients with scores in the top 5% were flagged for additional evaluation, we estimate that 1 in 6 would have dementia., Conclusion: The eRADAR tool uses existing EHR data to detect patients with good accuracy who may have unrecognized dementia. J Am Geriatr Soc 68:103-111, 2019., (© 2019 The American Geriatrics Society.)

Objectives: To examine the association between central nervous system (CNS)-active medication use and the risk of fall-related injury in community-dwelling older adults following dementia onset. Further, to evaluate increased risk at higher doses or with a greater number of CNS-active medication classes., Methods: Participants included community-dwelling older adults aged 65 years and older with a dementia diagnosis participating in the Adult Changes in Thought Study. From automated pharmacy data, a time-varying composite measure of CNS-active medication use was created. Central nervous system-active medication use was classified as current (use within prior 30 days), recent (prior 31-90 days), past (prior 91-365 days), and nonuse (no exposure in prior year). For current users, standardized daily doses (SDDs) were calculated for each CNS-active medication and summed across medications, and the number of CNS-active medication classes used was also measured. The outcome was fall-related injury based on emergency department, inpatient, and outpatient International Classification of Diseases, Ninth Revision (ICD-9) and external cause of injury (E) codes., Results: Among 793 subjects, 303 fall-related injuries occurred over a mean follow-up of 3.7 years (2907 total person-years). Relative to nonuse, fall risk was significantly higher for current use (adjusted hazard ratio [HR] 1.59, 95% confidence internal [CI] 1.19-2.12) but not for past or recent use. Among current users, increased risk was seen across SDD levels: HRs (95% CI): 1.77 (1.19-2.62), 1.79 (1.25-2.56), and 1.35 (0.96-1.92) for less than 1 SDD, 1 to less than 2 SDDs, and 2 or more SDDs, respectively (trend test, p=0.14). A trend was seen for increasing risk with a greater number of CNS-active medication classes; however, this was not statistically significant (trend test, p=0.084)., Conclusions: Current use of CNS-active medications was associated with fall-related injury in community-dwelling older adults followed from time of dementia onset, with increased risk even with use of low doses., (© 2019 Pharmacotherapy Publications, Inc.)

Objective: In this study, we assessed patient knowledge, beliefs, and attitudes about brain health and strategies for Alzheimer's disease and related dementias (ADRD) prevention. Methods: We administered a Web-based survey consisting of 17 questions about brain health and strategies for ADRD prevention in a convenience sample of 1661 patients in an integrated healthcare delivery system in Washington state between February and March 2018. We calculated frequency distributions of the quantitative data and conducted inductive content analysis of qualitative data. Results: Most respondents were female (77%), 51-70 years of age (64%), and white (89%). Although most agreed it is possible to improve brain health and reduce personal ADRD risk, one- third lacked confidence that they could take action to reduce personal ADRD risk. Participants' responses to open-ended questions revealed 10 themes grouped into 3 organizing categories regarding their perceptions about how to prevent ADRD onset: (1) understand ADRD; (2) stay engaged; and (3) manage one's own health and healthcare. Conclusions: Survey respondents were engaged and aware of dementia prevention, but they lacked access to personally action- able evidence..

Background: Detecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not., Methods: We analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ≥65 years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up - 3 years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3 years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia., Results: Four trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n = 1877, 36.6% cases, 45.5% controls), high (n = 1840, 43.2% cases, 44.1% controls), moderate (n = 365, 18.5% cases, 8.0% controls) and early poor adherence (n = 100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n = 1004, 75.0% cases, 79.0% controls), moderate (n = 192, 19.6% cases, 14.4% controls), early poor (n = 43, 2.0% cases, 3.5% controls), and delayed poor adherence (n = 40, 3.4% cases, 3.1% controls). No association was detected between statin adherence trajectories and dementia., Conclusions: Patterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia.

We administered a mixed-method survey to 1,661 patients in a large health system to assess preferences toward antihypertensive use for dementia prevention. If a specific antihypertensive medication was shown to prevent or delay dementia, the vast majority (>90%) of respondents currently taking an antihypertensive reported that they would be willing to take that specific antihypertensive starting as early as mid-life. Concerns reported were potential side effects, lack of evidence of effectiveness, blood pressure being normal or low, and medication cost. Analysis of free-text responses revealed themes of concerns regarding evidence of effectiveness and health priorities.

Objectives: To identify prevalence and risk factors for exposure to drug-disease interactions included in the Healthcare Effectiveness Data and Information Set (HEDIS) Drug-Disease Interaction (Rx-DIS) measure., Design: Cross-sectional retrospective database analysis., Setting: Outpatient clinics within the Department of Veterans Affairs (VA)., Participants: Individuals aged 65 and older who received VA outpatient care between October 1, 2003, and September 30, 2006., Measurements: Rx-DIS exposure based on the HEDIS measure was identified in VA patients with dementia, falls, and chronic renal failure using VA pharmacy and administrative databases. Factors associated with Rx-DIS exposure were examined, including demographic, health status, and access-to-care factors, including VA outpatient health services use and copayment status., Results: Of the 305,041 older veterans who met criteria for inclusion, the 1-year prevalence of Rx-DIS exposure was 15.2%; prevalence was 20.2% for dementia, 16.2% for falls, and 8.5% for chronic renal failure. Patients with high disease burden (physical, psychiatric, number of medications) were significantly more likely to have Rx-DIS exposure, regardless of condition. Hispanics and individuals with no copayments were more likely to have Rx-DIS exposure than whites or those with required copayments. There was variation in other predictors based on the type of Rx-DIS., Conclusion: The prevalence of Rx-DIS was common in older VA outpatients. Future studies should examine the risk of Rx-DIS exposure on health outcomes using separate analyses for each type of Rx-DIS separately before combining all Rx-DIS into a single measure of exposure. Studies that examine the effectiveness of interventions to reduce Rx-DIS exposure will also be helpful in improving the quality of care for older adults., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

We administered a web-based survey to a convenience sample of 561 patients in a large health system to assess patient attitudes toward dementia prevention in the context of designing a multi-domain Alzheimer's risk reduction intervention. The majority of respondents reported being very concerned about Alzheimer's disease, wanted to know their personal risk factors, and were highly motivated to make healthy lifestyle changes to lower dementia risk. The areas they were most interested in targeting to reduce dementia risk included physical activity, cognitive stimulation, nutrition, and sleep. These results provided strong support for our conceptual framework to target higher-risk patients with a personalized risk reduction strategy.

Background/objectivesGuideline-based management of cardiovascular disease often involves prescribing multiple medications, which contributes to polypharmacy and risk for adverse drug events in older adults. Deprescribing is a potential strategy to mitigate these risks. We sought to characterize and compare clinician perspectives regarding deprescribing cardiovascular medications across three specialties.DesignNational cross-sectional survey.SettingAmbulatory.ParticipantsRandom sample of geriatricians, general internists, and cardiologists from the American College of Physicians.MeasurementsElectronic survey assessing clinical practice of deprescribing cardiovascular medications, reasons and barriers to deprescribing, and choice of medications to deprescribe in hypothetical clinical cases.ResultsIn each specialty, 750 physicians were surveyed, with a response rate of 26% for geriatricians, 26% for general internists, and 12% for cardiologists. Over 80% of respondents within each specialty reported that they had recently considered deprescribing a cardiovascular medication. Adverse drug reactions were the most common reason for deprescribing for all specialties. Geriatricians also commonly reported deprescribing in the setting of limited life expectancy. Barriers to deprescribing were shared across specialties and included concerns about interfering with other physicians' treatment plans and patient reluctance. In hypothetical cases, over 90% of physicians in each specialty chose to deprescribe when patients experienced adverse drug reactions. Geriatricians were most likely and cardiologists were least likely to consider deprescribing cardiovascular medications in cases of limited life expectancy (all P

Informants' reports can be useful in screening patients for future risk of dementia. We aimed to determine whether informant-reported sleep disturbance is associated with incident dementia, whether this association varies by baseline cognitive level and whether the severity of informant-reported sleep disturbance is associated with incident dementia among those with sleep disturbance. A longitudinal retrospective cohort study was conducted using the uniform data set collected by the National Alzheimer's Coordinating Center. Older adults without dementia at baseline living with informants were included in analysis. Cox proportional hazards models showed that participants with an informant-reported sleep disturbance were more likely to develop dementia, although this association may be specific for older adults with normal cognition. In addition, older adults with more severe sleep disturbance had a higher risk of incident dementia than those with mild sleep disturbance. Informant-reported information on sleep quality may be useful for prompting cognitive screening. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a risk factor for Alzheimer's disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC).Objective: This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications.Methods: Descriptive analysis of ADNC for Adult Changes in Thought (ACT) Study autopsy cohort who used diabetes medications, including sulfonylureas, insulin, and biguanides; total N = 118. ADNC included amyloid plaque distribution (Thal phasing), neurofibrillary tangle (NFT) distribution (Braak stage), and cortical neuritic plaque density (CERAD score). We also examined quantitative measures of ADNC using the means of standardized Histelide measures of cortical PHF-tau and Aβ1-42. Adjusted analyses control for age at death, sex, education, APOE genotype, and diabetes complication severity index.Results: Adjusted analyses showed no significant association between any drug class and traditional neuropathologic measures compared to nonusers of that class. In adjusted Histelide analyses, any insulin use was associated with lower mean levels of Aβ1-42 (-0.57 (CI: -1.12, -0.02)) compared to nonusers. Five years of sulfonylureas and of biguanides use was associated with lower levels of Aβ1-42 compared to nonusers (-0.15 (CI: -0.28, -0.02), -0.31 (CI: -0.54, -0.07), respectively).Conclusion: Some evidence exists that diabetes medications are associated with lower levels of Aβ1-42, but not traditional measures of neuropathology. Future studies are needed in larger samples to build understanding of the mechanisms between diabetes, its medications, and ADRD, and to potentially repurpose existing medications for prevention or delay of ADRD. [ABSTRACT FROM AUTHOR]

Background: Medication management requires complex cognitive functioning, and therefore, difficulty taking medications might be an early sign of cognitive impairment and could be a risk factor for Alzheimer's disease and related dementias (ADRD). Accordingly, people with difficulty taking medications may benefit from more detailed cognitive screening, potentially aiding in the diagnosis of ADRD, which is underdiagnosed. We are unaware of evidence on medication management difficulties that precede a real-world ADRD diagnosis in the USA. Objective: Examine the association between difficulty taking medications and subsequent real-world ADRD diagnoses. Design: Case-control study, using Health and Retirement Study (HRS) survey data linked to Medicare claims. Participants: A total of 1461 HRS respondents with an ADRD diagnosis observed from 1993 to 2012 (cases), matched by year of birth, wave of HRS entry, and sex to 3771 controls with no ADRD diagnosis. Main Measures: We examined the association between diagnosis of ADRD and self-reported difficulty taking medications in the preceding years (1–2 and 3–4 years prior to case definition). Control individuals were assigned the index date from their matched case. Conditional logistic regressions adjusted for age, sex, race, education, and comorbidities. Key Results: Compared with matched controls, cases had higher prevalence of difficulty taking medications 1–2 years prior to diagnosis (11.0% versus 2.3%), and 3–4 years prior to diagnosis (5.8% versus 2.3%). Adjusted analyses showed that compared with individuals without ADRD, those with an ADRD diagnosis had more than four times higher odds of difficulty taking medications 1–2 years prior (OR = 4.56 (CI 3.30–6.31)), and more than two times higher odds of difficulty taking medications 3–4 years prior (OR = 2.41 (CI 1.61–3.59)). Conclusions: Odds of medication difficulty 1–2 years prior were more than four times greater for individuals with ADRD diagnoses compared with those without ADRD. Medication management difficulties may prompt further cognitive screening, potentially aiding in earlier recognition of ADRD. [ABSTRACT FROM AUTHOR]

Purpose: Antihypertensives may have effects on the brain beyond blood pressure lowering. Ongoing clinical trials aim to evaluate the effectiveness of approved antihypertensives in preventing dementia, including patients with and without hypertension. In order for a dementia prevention strategy using antihypertensives to be effective, it is critical to understand patient concerns about this strategy in both users and non-users of antihypertensives. Thus, this study examined the association between current use of antihypertensive and having concerns about using an antihypertensive as a dementia prevention strategy, as well as sociodemographic factors associated with concerns. Patients and methods: Cross-sectional,  self-administered, web-based survey was conducted among 1661 patients in a large health system in January 2018. Participants reported whether they were currently taking an antihypertensive (yes/no), and what types of hypothetical concerns they have about the idea of taking an antihypertensive to prevent dementia (yes/no, for each of 7 concerns). Associations between the two variables were assessed via logistic regression, and odds ratios with 95% confidence intervals were calculated. Results: Most respondents were female (77%), 51–70 years of age (64%), and white (89%), with 30% reporting current antihypertensive use. Compared to current users, non-users were more likely to report the five following concerns: side effects from the medication, hassle to take medications, lack of evidence, not wanting to use medications, and already having normal/low blood pressure. Non-users were also less likely to report having no concerns (adjusted OR = 0.3; 95% CI = 0.2–0.4) compared to current users. Younger age and lower income were associated with having more concerns. Conclusion: Patients not currently using an antihypertensive are more likely to have concerns about using an antihypertensive for dementia prevention, compared to current antihypertensive users. Patient perspectives are important to consider for the implementation of dementia prevention strategies. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate associations between high‐density lipoprotein cholesterol (HDL) and non‐HDL‐C levels at specific ages and subsequent Alzheimer's disease (AD) risk. Design Prospective population‐based cohort study. Setting: Adult Changes in Thought (ACT) Study. Participants: Individuals aged 65 and older with no dementia at ACT Study entry. We identified separate, partially overlapping subcohorts of ACT participants who were eligible for each age band–specific analysis (50–59, n = 1,088; 60–69, n = 2,852; 70–79, n = 2,344; 80–89, n = 537). Measurements Exposure consisted of clinical measures of total cholesterol (TC) and HDL‐C from laboratory data during a given age band. Outcomes of incident AD were assessed post‐age band using standard research diagnostic criteria. Statistical analyses used adjusted Cox proportional hazards regression models for each exposure and outcome pair within an age band. Cholesterol exposures were modeled using cubic splines. Results: For non‐HDL‐C, we found a statistically significant association with AD risk in the 60 to 69 (omnibus p =.005) and 70 to 79 (omnibus p =.04) age bands, suggesting a potential U‐shaped relationship (greater risk at low and high levels). For example, in people aged 60 to 69, those with an average non‐HDL‐C level of 120 mg/DL had a 29% greater AD hazard (hazard ratio (HR)=1.29, 95% confidence interval (CI)=1.04–1.61) than those with an average non‐HDL‐C level of 160 mg/dL, whereas those with an average non‐HDL‐C level of 210 mg/dL had a 16% greater hazard (HR=1.16, 95% CI=1.01–1.33). We did not find a statistically significant association between HDL‐C and AD risk. Conclusion: People with low (120 mg/dL) and high (210 mg/dL) non‐HDL‐C levels during their 60s and 70s had modestly higher risk of AD than those with intermediate (160 mg/dL) levels. The extreme age bands (50s and 80s) had small sample sizes. J Am Geriatr Soc 66:2344–2352, 2018. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the rates of healthcare utilization among patients who developed dementia while enrolled in the Adult Changes in Thought (ACT) research between 1994 and 2014. The variables considered include patients with diagnosed and undiagnosed dementia, number of outpatient visits, emergency department visits and hospitalizations. The correlation between dementia and comorbidity is assessed.

Objectives To describe facility-level variation in two measures of potentially inappropriate prescribing prevalent in Veterans Affairs ( VA) facilities-exposure to high-risk medications in elderly adults ( HRME) and drug-disease interactions ( Rx- DIS)-and to identify facility characteristics associated with high-quality prescribing. Design Cross-sectional. Setting VA Healthcare System. Participants Veterans aged 65 and older with at least one inpatient or outpatient visit in 2005-2006 ( N = 2,023,477; HRME exposure) and a subsample with a history of falls or hip fractures, dementia, or chronic renal failure (n = 305,059; Rx- DIS exposure). Measurements Incident use of any HRME ( iHRME) and incident Rx- DIS ( iRx- DIS) and facility-level rates and facility-level predictors of iHRME and iRx- DIS exposure, adjusting for differences in patient characteristics. Results Overall, 94,692 (4.7%) veterans had iHRME exposure. At the facility level, iHRME exposure ranged from 1.6% at the lowest facility to 12.8% at the highest (median 4.7%). In the subsample, 9,803 (3.2%) veterans had iRx-DIS exposure, with a facility-level range from 1.3% to 5.8% (median 3.2%). In adjusted analyses, veterans seen in facilities with formal geriatric education had lower odds of iHRME (odds ratio ( OR) = 0.86, 95% confidence interval ( CI) = 0.77-0.96) and iRx- DIS ( OR = 0.95, 95% CI = 0.88-1.01). Patients seen in facilities caring for fewer older veterans had greater odds of iHRME ( OR = 1.54, 95% CI = 1.35-1.75) and iRx- DIS exposure ( OR = 1.22, 95% CI = 1.11-1.33). Conclusion Substantial variation in the quality of prescribing for older adults exists across VA facilities, even after adjusting for patient characteristics. Higher-quality prescribing is found in facilities caring for a larger number of older veterans and facilities with formal geriatric education. [ABSTRACT FROM AUTHOR]

Background: Detecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not. Methods: We analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ≥ 65 years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up -3 years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3 years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia. Results: Four trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n = 1877, 36.6% cases, 45.5% controls), high (n = 1840, 43.2% cases, 44.1 % controls), moderate (n = 365, 18.5% cases, 8.0% controls) and early poor adherence (n = 100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n = 1004, 75.0% cases, 79.0% controls), moderate (n = 192, 19.6% cases, 14.4% controls), early poor (n = 43, 2.0% cases, 3.5% controls), and delayed poor adherence (n = 40, 3.4% cases, 3.1 % controls). No association was detected between statin adherence trajectories and dementia. Conclusions: Patterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia. [ABSTRACT FROM AUTHOR]